THE DETERMINANTS OF GLYCEMIC RESPONSES TO DIET RESTRICTION AND WEIGHT-LOSS IN OBESITY AND NIDDM

OBJECTIVE - To examine the mechanisms by which weight loss improves gl ycemic control in overweight subjects with NIDDM, particularly the rel ationships between energy restriction, improvement in insulin sensitiv ity, and regional and overall adipose tissue loss. RESEARCH DESIGN AND METHODS - Hyperinsulinemic glucose clamps were performed in 20 subjec ts (BMI = 32.0 +/- 0.5 [SEM] kg/m(2), age = 48.4 +/- 2.7 years) with n ormal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before a nd on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 +/- 250 [SD] kcal/day) formula diet. Body composition changes were assesse d by dual energy x-ray absorptiometry and insulin secretory changes we re measured by insulin response to intravenous glucose before and afte r weight loss. RESULTS - In both groups, energy restriction (d4) reduc ed fasting plasma glucose (FPG) (Delta FPG: NGT = -0.4 +/- 0.2 mmol/l and NIDDM = -1.1 +/- 0.03 mmol/l, P = 0.002), which was independently related to reduced carbohydrate intake (partial r = 0.64, P = 0.003). There was a marked d4 increase in percent of insulin suppression of he patic glucose output (HGO) in both groups (Delta HGO suppression: NGT = 28 +/- 15% and NIDDM = 32 +/- 8%, P = 0.002). By d28, with 6.3 +/- 0 .4 kg weight loss, FPG was further reduced (d4 vs, d28) in NIDDM only (P = 0.05), and insulin sensitivity increased in both groups (P = 0.02 ). Only loss of abdominal fat related to improvements in FPG (r = 0.51 , P = 0.03) and insulin sensitivity after weight loss (r = 0.48, P = 0 .05). In contrast to insulin action, there were only small changes in insulin secretion. CONCLUSIONS - Both energy restriction and weight lo ss have beneficial effects on insulin action and glycemic control in o besity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects rela te to changes in abdominal fat.